Rhabdomyosarcoma radiotherapy indications and outcome
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RhabdomyosarcomaRadiotherapy: Indications and Outcome
Víctor BarrondoRadiation Oncology Department/Brachytherapy Section
Hospital Universitario Basurto, Bilbao
Intergroup Rhabdomyosarcoma
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IRS I (1972 – 1978) OS 55%IRS II (1978 – 1984) OS 63%IRS III (1984 – 1991) OS 71%IRS IV (1991 – 1997) OS 71%COG D9602,D9803, D9802 (1998…)
Intergroup Rhabdomyosarcoma Study
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Technology CostsBefore You get excited about the lowlow price for 10Mb data storage, makesure you read the ultra fine print. Turnsout the $3,495 price is for a refurbishedunit only. The new one retails for awhopping $4,495. Oh, and there isanother catch: the price is in 1980dollars (US). Adjusted to 2010 dollars,that comes to around $13,395*
*US Per Capita personal Income 1980: 9,500$
2010: 40,500$Source: U.S. Department of Commerce, Bureau of EconomicA n a l y s i s , S u r v e y o f C u r r e n t B u s i n e s s .h t tp : / / w w w. bea .gov /news re leases / re lsarch ivesp i .h tm
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Introduction
• Highly malignant neoplasm arising from embryonal mesenchyme• With capacity for skeletal muscle differentiation.• 40% of all soft tissue sarcomas and 7% childhood malignancies in the US
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• Histology• Stage
• Primary site (most important prognostic factor)• Tumor size• LN involvement (especially in extremities)• Metastatic disease
• Group• Extent of resection
Prognostic Factors
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M0N1≤5All Other Sites3
M1N0, N1Any SizeAny Site4
M0N0, N1>5All Other Sites
M0N0≤5All Other Sites2
M0N0, N1AnyOrbit, Non PM H&N, GU non bladder/prostate, biliary tract1
Distant MetastasesRegional Lymph NodesTumor Size (cm)SiteStage
Intergroup Rhabdomyosarcoma Study Group Presurgical Staging System
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Intergroup Rhabdomyosarcoma Study Group Surgical-Patologic Grouping System
Distant metastases present at diagnosisIV
Localized tumor, with gross residual disease after grossly incomplete removal, or biopsy only.III
Localized tumor, grossly removed with (a) microscopically involved margins, (b) involved grossly resectedregional lymph nodes, or (c) both.II
Localized tumor, completely removed with patologically clear margins and no regional lymph nodeinvolvement.I
DefinitionGroup
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Current Children’s Oncology Group (COG) Risk Groups
High4IVERMS
High4IVARMS
Intermediate1, 2, 3I, II, IIIARMS
Intermediate2, 3IIIERMS
Low (Subset B)2, 3I, IIERMS
Low (Subset A)1I, II, IIIERMS
Risk GroupStageGroupHistology
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Radiotherapy Indications
The Short Answer is…• Radiotherapy indicated in Group II-IV patients and Group I Alveolar histology.• As a result from COG D9803, RT recommended at an early time point (4 Week).
. Wolden SL, Anderson JR, Crist WM, et al. Indications for radiotherapy and chemotherapy after complete resection inrhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol 1999;17(11):3468e3475.
. Raney RB, Anderson JR, Brown KL, et al. Treatment results for patients with localized, completely resected (group I) alveolarrhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984e1997: a report from the Children’sOncology Group. Pediatr Blood Cancer 2010;55(4):612e616.
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Radiotherapy Doses COG D9602/D9803
Microscopic Residual Disease 3600 cGyResected Node Positive 4140 cGyOrbital Location Gross Disease 4500 cGyGross Residual Disease 5040 cGySecond Look accepted
IRS- IV: Hyperfractionation (59.4Gy / 1.1Gy fraction b.i.d.) did NOT improve local,regional or distant control over conventional fractionation for Group III tumors.
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Modern Radiotherapy Techniques: IMRT
• Early adopters since 1999.• The next step in radiation treatment planning after 3D.• Inverse planning with computer-assisted optimization.• Dose painting.
Sharp dose fall off outside target volume with selective avoidanceof critical structures and tissues
• Multiple Fields.Dose modulation within each field
• Better immobilization, longer treatment time.
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Modern Radiotherapy Techniques: IMRT
IMRT vs 3DCRT improved target dose coverage with no improvement in LC or FFS
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Modern Radiotherapy Techniques: IMRT
Smaller Margin: 15mm using MRI&PET fusion vs 20mm.LFR 3 years: 5% Parameningeal & 0% Orbit/H&N.
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• Standard doses with PNI for adolescentsand young adults (n=21) and reduced dosesper fraction for children (n=20).
• 16%-18% (median, 17%) decrease in themean dose for rectum, bladder and bowel.
• 90%LC (100% children, 79% young adults).
Modern Radiotherapy Techniques: IMRT
GEIS XIth International Symposium / Seville - November, 29th 2013
A) Anatomical planning target volume (PTV).
B) Biological PTV.
C) Fusion of anatomical and biological PTV.
D) Contour based optimization.
E) Voxel signal intensity based optimization.
IMRT Functional Dose painting
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Modern Radiotherapy Techniques: Protons
• Inelastic collisions through matter
• Large proportion of the energy at theBragg peak and then falls off
• Particular advantage in H&N wheresparing of critical structures may bebetter accomplished using protons,particularly in young children.
• Long-term clinical outcomes comparingproton therapy and IMRT not yetavailable.
• Cost concern.
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Modern Radiotherapy Techniques: Protons
• LF 18% vs 17% in the IRSII-IV despite poor prognostic features compared with theIRS trial population. (59% intracranial extension vs 38%) and median time to thestart of proton RT was 8 weeks (3/4LF late referral and ICE).
• Reduction in late effects compared with previously published series of patientstreated with photon RT (despite a higher proportion of younger patients).
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Favourable SitesOrbit Rhabdomyosarcoma
• Most commonly embryonal histology.• Small size.• Rarely lymph node involvement.• Standard treatment; QT+RT preserving eye.• 3 year FFS 89%, OS 100%, 5 year LC 98%.• Toxicity: Cataract, keratopathy, dry eye, loss of vision is rare.
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Favourable SitesGynaecological Rhabdomyosarcoma
• Good prognosis.• Common strategy: Initial QT with local therapy to remanent disease
(if present).• Surgery rate decreased from IRS I-IV.• Very good location for Brachytherapy.• 5 year OS 82%.
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Favourable SitesParatesticular Rhabdomyosarcoma
• Initial management with Radical inguinal orchiectomy +/- RLND(CT with enlarged nodes or 10 years or older patients).
• Avoid RT to scrotum to preserve contralateral testicular function ifcomplete resection achieved.
• 3 year FFS 90%.
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Unfavourable SitesExtremity or Trunk Rhabdomyosarcoma
• High rate of lymph node involvement, node sampling required.• Surgery maintaining form and function with RT preferred rather
than amputation.• 10 year OS 63%, FFS 57%.
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Unfavourable SitesParameningeal Rhabdomyosarcoma
• Intracraneal extension of disease main prognostic factor.• Surgery often limited (95% Group III).• 5 year OS 73%, FFS 69%, LC 83%.
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Take Home Messages
• Close collaboration mandatory.• Modern Radiotherapy techniques needed.• Work Hard.
GEIS XIth International Symposium / Seville - November, 29th 2013
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